Sanfilippo syndrome or Mucopolysaccharidosis III (MPS III) is an inherited lysosomal storage disease caused by mutations within the enzymes responsible for the degradation of heparan sulfate. MPS IIIA and B, the most prevalent subtypes, are caused by mutations of Heparan-N-sulfatase (SGSH) and N-acetyl-a-glucosaminidase (NAGLU), respectively. MPS IIIA and B show cognitive delay and regression symptoms around 1-3 years, followed by behavioural difficulties, hyperactivity, loss of motor function, intellectual processes, and premature death (Andrade et al., 2015; Valstar et al., 2008). Treatments used or in development for other forms of MPS, such as enzyme replacement therapy or gene therapy, are of limited use for MPS III due to the blood-brain barrier or the presence of antibodies against the vectors. Pharmacological chaperones, on the other hand, have shown potential as treatments for other lysosomal storage diseases. The availability of compound libraries, molecular modelling and crystal structures of both proteins allowed virtual screening for potential chaperones for MPS III. Using the compound library DrugBank, over 8800 compounds were docked into the enzymes’ active site and ranked according to the estimated binding affinity. Ten compounds were identified as potential pharmacological chaperones from this docking study. We are testing these compounds from a virtual screen against NAGLU, SGSH, and proteins with similar catalytic pockets to confirm the selectivity of the compounds and therefore assess the effectiveness of these compounds as possible treatments. Furthermore, structural characterisation methods will be applied in this project, with the binding being validated using x-ray crystallography and the mutant forms of the enzyme assessed with molecular dynamics simulations.